We conducted a randomized trial of dose-intensive weekly alternating chemotherapy (CAV/PE-W) and standard alternating chemotherapy (CAV/PE) in small cell lung cancer (SCLC) patients with good prognostic factors. A total of 76 patients with SCLC was randomized. The CAV/PE-W consisted of 4 alternating cycles of cyclophosphamide: 500 mg/m2, doxorubicin: 30 mg/m2, and vincristine: 1 mg/m2 (day 1) and cisplatin: 50 mg/m2 (day 8) and etoposide: 75 mg/m2 (days 8 and 9). The CAV/PE consisted of 2 alternating cycles of cyclophosphamide: 800 mg/m2, doxorubicin: 50 mg/m2, and vincristine: 1.4 mg/m2 (day 1), cisplatin: 100 mg/m2 (day 22) and etoposide: 100 mg/m2 (days 22, 23 and 24). Eligibility criteria were no prior therapy, no active concomitant malignancy, ECOG PS of 0 or 1, age < or =75, adequate hematologic functions and no brain metastasis. The complete response (CR) rate for CAV/PE-W (14/38, 36.8%) was significantly higher than that for CAV/PE (6/38, 15.8%, chi2; p=0. 032). However, the response rate in patients on CAV/PE-W (36/38, 94. 7%) was not significantly higher than the rate for CAV/PE (31/38, 81. 6%, chi2; p=0.076). Progression-free survival for patients on CAV/PE-W was significantly longer than that of patients on CAV/PE (41.4 weeks vs. 21.3 weeks, log-rank; p=0.0007, generalized Wilcoxon; p=0.0034) as was overall median survival (67.0 weeks vs. 51.2 weeks, log-rank; p=0.028). Actual dose-intensity of CAV/PE-W was 1.74 times that of CAV/PE. Hematological toxicities were equally frequent and G-CSF contributes to treatment efficacy by allowing administration of dose-intensive chemotherapy. The CAV/PE-W achieved a higher CR rate and longer survival, than the CAV/PE.

Adult↗

PubMedDate not supplied

Antiproliferative activity and mechanism of action of DZ-3358, a novel pyrimidinyl pyrazole derivative.

The novel pyrimidinyl pyrazole derivative, 1-[5-methyl-1-(2-pyrimidinyl) -4-pyrazolyl]-3-[4-(3-chlorophenyl)-1-piperazinyl]-1-trans-propene hydrochloride (DZ-3358), was found through random screening to exhibit anti-proliferative activity against human and murine cancer cell lines. DZ-3358 induced the mitotic arrest of P388 murine leukemia cells at 0.4 microgram/ml in a time-dependent manner, and inhibited porcine tubulin polymerization. Furthermore, using immunofluorescence techniques, we observed microtubule formation in NUGC-3 human gastric cancer cells treated with DZ-3358. Microtubule formation was disordered, similar to that which occurred when such cells were treated with colchicine. These findings suggest that the mechanism of the anti-proliferative effect of DZ-3358 is the inhibition of mitosis due to the blocking of tubulin polymerization. The differential pattern of growth inhibitory concentrations of DZ-3358 against a series of cancer cell lines was compared with that of colchicine and vincristine, and no correlation was found with the pattern of these two drugs. DZ-3358 may be useful as a new type of tubulin inhibitor and anti-cancer drug.

Animals↗

PubMedDate not supplied

Effect of OP-2507, a stable prostacyclin analogue on cerebral ischemia induced by unilateral ligation of common carotid artery in gerbils.

Effects of OP-2507 [15-cis-(4-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deoxy -9 alpha-nitrilo- PGF1 methylester] on cerebral ischemia induced by unilateral ligation of common carotid artery in gerbils were investigated with reference to behavioral and neuropathological changes. A good coincidence between neurological symptoms and neuropathological changes was observed in gerbils after unilateral ligation of common carotid artery as revealed by the high percentage of coincidence (90% of total animals). All gerbils which showed neurological symptoms, either circling behavior or rolling fit, had cerebral infarction in their ipsilateral hemisphere. In these animals, neuropathological changes of cerebral regions were observed in cortex, corpus callosum, hippocampus, basal ganglia, interbrain and midbrain, in contrast with medulla oblongata and cerebellum which did not show any neuropathological changes. Pretreatment with a dose range of 1-30 micrograms/kg, s.c. of OP-2507 showed a protective effect in the occurrence of neurological symptoms, such as circling behavior and rolling fit, in a dose-dependent manner. The effect of OP-2507 was also confirmed in neuropathological examination which was performed with observation of neurological deficits in the same animals. The severity of cerebral infarction of all brain regions was significantly prevented by treatment with OP-2507. The results suggested that the protective effect of OP-2507 on regional infarction gave apparent protection against the occurrence of neurological deficits for this compound.

Animals↗

PubMedDate not supplied

Inhibition of tumor cell invasion in the Boyden chamber assay by a mannosidase inhibitor, mannostatin A.

An alpha-mannosidase inhibitor, mannostatin A, from Streptoverticillium verticillus var. quintum inhibited chemotactic invasion of mouse B16/F10 melanoma cells in the Boyden chamber assay. It also inhibited in vitro invasion of K-ras-NIH3T3 cells. Mannostatin A did not inhibit the growth of either cell line at the concentration effective to inhibit invasion. Addition of mannostatin A to the cultured B16/F10 or K-ras-NIH3T3 cells inhibited cellular alpha-mannoside activity specifically. Mannostatin A-treated B16/F10 cells also showed decreased metastatic activity in vivo in C57Bl/6 mice.

3T3 Cells↗